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Introduction: Low self‐esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self‐esteem show a distinct neural pathophysiology. Previous studies linked low self‐esteem to reduced task‐induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya‐Maldonado et al. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self‐esteem. Methods: Eighty‐three MDD patients performed the desire–reason dilemma task and completed the Rosenberg Self‐Esteem Scale (RSES). Brain activity during bottom‐up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery–Åsberg Depression Rating Scale. To corroborate the findings, we compared self‐esteem scores between patient subgroups with impaired task‐induced deactivation (n = 31) and with preserved task‐induced deactivation (n = 31) of the pgACC. Results: Consistent with our a priori hypothesis, activity in a bilateral fronto‐striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task‐induced pgACC deactivation showed lower self‐esteem (t (52.82) = −2.27; p =.027, d = 0.58) compared to those with preserved task‐induced pgACC deactivation. Conclusions: We conclude that low self‐esteem in MDD patients is linked to a task‐induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self‐esteem. [ABSTRACT FROM AUTHOR]

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro . In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM 0B ) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM 2B-0B ) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM 2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance. [ABSTRACT FROM AUTHOR]

Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging. Hum Brain Mapp 35:4488-4498, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Human neuroimaging studies have well demonstrated the presence of a “default system” in the brain, which shows a “default mode of brain activity”, i.e., greater activity during the resting state than during an attention-demanding cognitive task. The default system consists mainly of the medial prefrontal and medial parietal areas. It has been proposed that this default activity is concerned with internal thought processes. Here, I first describe activities observed in the human default system measured by several methods, in relation task performance, development, aging and psychiatric disorder. I will then introduce recent nonhuman primate studies that indicate correlated low-frequency spontaneous brain activity within the default system, high metabolic levels in these medial brain areas during rest and task-induced suppression of neuronal activity in the medial parietal area. Furthermore, I will present our data in which we found task-induced deactivation in the monkey default system, and will examine similarities and differences in default activity between the human and nonhuman primate. Finally, I will discuss the functional significance of the default system and consider the possibility of internal thought processes in the monkey. [Copyright &y& Elsevier]

Rationale: The default mode network (DMN) is a functional network which is implicated in a range of cognitive processes. This network is proposed to consist of hubs located in the ventromedial prefrontal cortex (vmPFC), posterior cingulate/retrosplenial cortex (PCC/rSpl), and inferior parietal lobule (IPL), with other midline cortical and temporal lobe nodes connected to these hubs. How this network is modulated by neurochemical systems during functional brain activity is not yet understood. Objectives: In the present study, we used the norepinephrine/dopamine transporter inhibitor modafinil to test the hypothesis that this drug modulates the DMN. Methods: Eighteen healthy right-handed adults participated in a double-blind, placebo-controlled study of single oral dose modafinil 200 mg. They performed a simple visual sensorimotor task during slow event-related fMRI. Drug effects were interrogated within the DMN defined by task-induced deactivation (TID) on placebo. Results: There was a trend toward faster reaction time (RT) on modafinil (Cohen's d = 0.38). Brain regions within the DMN which exhibited significant modafinil-induced augmentation of TID included vmPFC, PCC/rSpl, and left IPL. Across subjects, the modafinil effect on TID in the vmPFC was significantly and specifically associated with drug effects on RT speeding. Conclusions: Modafinil augments TID in the DMN to facilitate sensorimotor processing speed, an effect which may be particularly dependent on changes in vmPFC activity. This is consistent with the gain control function of catecholamine systems and may represent an important aspect of the pro-cognitive effects of modafinil. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia in old age, and is characterized by prominent impairment of episodic memory. Recent functional imaging studies in AD have demonstrated alterations in a distributed network of brain regions supporting memory function, including regions of the default mode network. Previous positron emission tomography studies of older individuals at risk for AD have revealed hypometabolism of association cortical regions similar to the metabolic abnormalities seen in AD patients. In recent functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain default mode regions have also been found to demonstrate an abnormal fMRI task-induced deactivation response pattern. That is, the relative decreases in fMRI signal normally observed in the default mode regions in healthy subjects performing a cognitive task are not seen in AD patients, or may even be reversed to a paradoxical activation response. Our recent studies have revealed alterations in the pattern of deactivation also in elderly individuals at risk for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement with recent reports from other groups, these studies demonstrate that the pattern of fMRI task-induced deactivation is progressively disrupted along the continuum from normal aging to MCI and to clinical AD and more impaired in e4 carriers compared to non-carriers. These findings will be discussed in the context of current literature regarding functional imaging of the default network in AD and at-risk populations. [ABSTRACT FROM AUTHOR]

Abstract: Task-induced deactivation is frequently reported in the ventro-medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), regions considered to belong to the default mode network. To investigate the effect of dopamine on task-induced deactivation, we used positron emission tomography to measure cerebral blood flow during performance of the Tower of London task before and after administration of the dopamine receptor agonist apomorphine in six healthy volunteers (49–66 years old) and six Parkinson disease patients (52–69 years old). Although task-induced deactivation was observed in the vmPFC and PCC in both groups and in both conditions, an inverse correlation between activation and problem complexity was observed in the vmPFC only in the apomorphine condition. [Copyright &y& Elsevier]

Abstract: The regions that comprise the functionally connected resting-state default-mode network (DMN) in adults appear to be the same as those that are characterized by task-induced decreases in blood-oxygen-level-dependent (BOLD) signal. Independent component analysis can be used to produce a picture of the DMN as an individual rests quietly in the scanner. Contrasts across conditions in which cognitive load is parametrically modulated can delineate neural structures that have decreases in activation in response to high-demand task conditions. Examination of the degree to which these networks subsume dissociable brain substrates, and of the degree to which they overlap, provides insight concerning their purpose, function, and the nature of their associations. Few studies have examined the DMN in children, and none have tested whether the neural regions that comprise the DMN during a resting condition are the same regions that show reduced activity when children engage in cognitive tasks. In this paper we describe regions that show both task-related decreases and spontaneous intrinsic activity at rest in children, and we examine the co-localization of these networks. We describe ways in which the DMN in 7–12-year-old children is both similar to and different from the DMN in adults; moreover, we document that task-induced deactivations and default-mode resting-state activity in children share common neural substrates. It appears, therefore, that even before adolescence a core aspect of task-induced deactivation involves reallocating processing resources that are active at rest. We describe how future studies assessing the development of these systems would benefit from examining these constructs as part of one continuous system. [Copyright &y& Elsevier]

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task. [ABSTRACT FROM AUTHOR]

Abstract: In functional neuroimaging, a local decrease in blood flow during an active task, relative to a “resting” baseline, is referred to as task-induced deactivation (TID). TID may occur when resources shift from ongoing, internally generated processing typical of “resting” states to processing required by an exogenous task. We previously found specific brain regions in which TID increased as task processing demands increased. When engaged in an exogenous cognitive task, reallocation of resources from areas involved in internal processing should result in suspension of that processing. Self-reported thought content has been used as an indicator of the extent of internal processing activity. We investigated the relationship between TID and task-unrelated thought (TUT) frequency using an auditory target detection task with seven levels of task difficulty. At varied intervals during task performance, subjects indicated whether they were experiencing a TUT. We expected TUT frequency to decrease as task demands increased and for this pattern to correlate with TID magnitude across conditions. Generally, fewer TUTs were reported during difficult task conditions than during easier conditions. As TID magnitude increased across task conditions, the frequency of TUTs declined (r = 0.90, P = 0.005). Four left hemisphere regions (posterior parieto-occipital cortex, anterior cingulate gyrus, fusiform gyrus, and middle frontal gyrus) showed strong relationships between TUTs and TID (r > 0.79, P < 0.05 corrected). As these regions have been implicated in semantic processing and self-referential thought, the findings support the suspension of internal cognitive processing as one mechanism for TID. [Copyright &y& Elsevier]

The anterior cingulate cortex (ACC) participates in both performance optimization and evaluation, with dissociable contributions from dorsal (dACC) and rostral (rACC) regions. Deactivation in rACC and other default-mode regions is important for performance optimization, whereas increased rACC and dACC activation con- tributes to performance evaluation. Errors activate both rACC and dACC. We propose that this activation reflects differential error- related involvement of rACC and dACC during both performance optimization and evaluation, and that these two processes can be distinguished by the timing of their occurrence within a trial. We compared correct and error antisaccade trials. We expected errors to correlate with an early failure of rACC deactivation and in- creased activation of both rACC and dACC later in the trial. Eighteen healthy subjects performed a series of prosaccade and antisaccade trials during event-related functional MRI. We estimated the hemodynamic responses for error and correct antisaccades using a finite impulse-response model. We examined ACC activity by comparing error and correct antisaccades with a fixation baseline and error to correct antisaccades directly. Compared with correct antisaccades, errors were characterized by an early bilateral failure of deactivation of rACC and other default-mode regions. This difference was significant in rACC. Errors also were associated with increased activity in both rACC and dACC later in the trial. These results show that accurate performance involves deactivation of the rACC and other default mode regions and suggest that both rACC and dACC contribute to the evaluation of error responses. [ABSTRACT FROM AUTHOR]